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Phenotypes of a female patient with novel de novo frameshift ARX variant identified by whole-exome sequencing: a case report
Variants in the aristaless-related homeobox (ARX) gene cause a diverse spectrum of phenotypes of neurodevelopmental disorders (NDD) in male patients. This article describes the role of genetic testing using whole-exome sequencing (WES) in detecting a novel de novo frameshift variant in the ARX gene...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9949785/ https://www.ncbi.nlm.nih.gov/pubmed/36845779 http://dx.doi.org/10.1097/MS9.0000000000000197 |
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author | Iskandar, Kristy Herini, Elisabeth S. Triono, Agung Hadiyanto, Marissa L. Nugrahanto, Andika P. Gunadi, |
author_facet | Iskandar, Kristy Herini, Elisabeth S. Triono, Agung Hadiyanto, Marissa L. Nugrahanto, Andika P. Gunadi, |
author_sort | Iskandar, Kristy |
collection | PubMed |
description | Variants in the aristaless-related homeobox (ARX) gene cause a diverse spectrum of phenotypes of neurodevelopmental disorders (NDD) in male patients. This article describes the role of genetic testing using whole-exome sequencing (WES) in detecting a novel de novo frameshift variant in the ARX gene in a female patient with autism, seizure, and global developmental delay. CASE PRESENTATION: A 2-year-old girl with frequent seizures, global developmental delay, and autistic features was referred to our hospital. She was the second child of consanguineous non-affected parents. She had a high forehead, mildly prominent ears, and prominent nasal root. A generalized epileptiform discharge was noted in her electroencephalography. Brain MRI revealed corpus callosum agenesis, cerebral atrophy, and a left parafalcine cyst. The WES result showed a likely pathogenic variant identified as a novel de novo deletion in exon 4 of the ARX gene, which creates a frameshift variant. The patient is on dual therapy of antiepilepsy drugs, physiotherapy, speech therapy, occupational therapy, and oral motor exercises. CLINICAL DISCUSSION: Variants in the ARX gene can result in various phenotypes in males transmitted from asymptomatic carrier females. However, several reports showed that the ARX variants might cause phenotypes in females with milder symptoms than affected males. CONCLUSION: We report a novel de novo ARX variant in an affected female with a NDD. Our study confirms that the ARX variant might cause remarkable pleiotropy phenotypes in females. Moreover, WES could help to identify the pathogenic variant in NDD patients with diverse phenotypes. |
format | Online Article Text |
id | pubmed-9949785 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-99497852023-02-24 Phenotypes of a female patient with novel de novo frameshift ARX variant identified by whole-exome sequencing: a case report Iskandar, Kristy Herini, Elisabeth S. Triono, Agung Hadiyanto, Marissa L. Nugrahanto, Andika P. Gunadi, Ann Med Surg (Lond) Case Reports Variants in the aristaless-related homeobox (ARX) gene cause a diverse spectrum of phenotypes of neurodevelopmental disorders (NDD) in male patients. This article describes the role of genetic testing using whole-exome sequencing (WES) in detecting a novel de novo frameshift variant in the ARX gene in a female patient with autism, seizure, and global developmental delay. CASE PRESENTATION: A 2-year-old girl with frequent seizures, global developmental delay, and autistic features was referred to our hospital. She was the second child of consanguineous non-affected parents. She had a high forehead, mildly prominent ears, and prominent nasal root. A generalized epileptiform discharge was noted in her electroencephalography. Brain MRI revealed corpus callosum agenesis, cerebral atrophy, and a left parafalcine cyst. The WES result showed a likely pathogenic variant identified as a novel de novo deletion in exon 4 of the ARX gene, which creates a frameshift variant. The patient is on dual therapy of antiepilepsy drugs, physiotherapy, speech therapy, occupational therapy, and oral motor exercises. CLINICAL DISCUSSION: Variants in the ARX gene can result in various phenotypes in males transmitted from asymptomatic carrier females. However, several reports showed that the ARX variants might cause phenotypes in females with milder symptoms than affected males. CONCLUSION: We report a novel de novo ARX variant in an affected female with a NDD. Our study confirms that the ARX variant might cause remarkable pleiotropy phenotypes in females. Moreover, WES could help to identify the pathogenic variant in NDD patients with diverse phenotypes. Lippincott Williams & Wilkins 2023-02-07 /pmc/articles/PMC9949785/ /pubmed/36845779 http://dx.doi.org/10.1097/MS9.0000000000000197 Text en © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License 4.0 (https://creativecommons.org/licenses/by/4.0/) (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) |
spellingShingle | Case Reports Iskandar, Kristy Herini, Elisabeth S. Triono, Agung Hadiyanto, Marissa L. Nugrahanto, Andika P. Gunadi, Phenotypes of a female patient with novel de novo frameshift ARX variant identified by whole-exome sequencing: a case report |
title | Phenotypes of a female patient with novel de novo frameshift ARX variant identified by whole-exome sequencing: a case report |
title_full | Phenotypes of a female patient with novel de novo frameshift ARX variant identified by whole-exome sequencing: a case report |
title_fullStr | Phenotypes of a female patient with novel de novo frameshift ARX variant identified by whole-exome sequencing: a case report |
title_full_unstemmed | Phenotypes of a female patient with novel de novo frameshift ARX variant identified by whole-exome sequencing: a case report |
title_short | Phenotypes of a female patient with novel de novo frameshift ARX variant identified by whole-exome sequencing: a case report |
title_sort | phenotypes of a female patient with novel de novo frameshift arx variant identified by whole-exome sequencing: a case report |
topic | Case Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9949785/ https://www.ncbi.nlm.nih.gov/pubmed/36845779 http://dx.doi.org/10.1097/MS9.0000000000000197 |
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